Abstract Caring for a loved one with dementia is a highly meaningful part of family life; however, the associated burden and strain can have adverse consequences for caregivers including increased mental and physical health problems, reduced well-being, and increased mortality. For the past 15 years, our multidisciplinary group (psychology, neurology, nursing) has collaborated on a program project grant (AG19724) focused on patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD). Five years ago, we began a new program of research studying the familial caregivers of these patients (AG41762). Because AD and FTD target different neural networks, they produce deficits in functioning that create different challenges for caregivers. AD patients typically present with losses in cognitive domains (e.g., memory, visuospatial ability), with emotional functioning relatively preserved. FTD patients, in contrast, typically present with deficits in emotional functioning (e.g., coldness, lack of empathy, apathy, personality changes), with many cognitive abilities relatively preserved. The proposed research expands our study of emotional factors in caregivers, patients, and patient-caregiver relationships that are associated with the adverse effects of caregiving. We will recruit 300 new participants (50 patients with AD and 50 patients with FTD and their spousal caregivers, 50 neurologically healthy controls and their spouses). Emotional functioning will be evaluated in three domains: (a) emotional reactivity (responding to emotional stimuli), (b) emotion regulation (adjusting emotional responses to personal and situational demands), and (c) emotional recognition (recognizing emotions in others). Adverse effects of caregiving will be assessed using well-established measures of burden, illness, and well-being. The research addresses four specific aims: Aim 1 (Predictors): To determine how specific emotional characteristics of patients, caregivers, and patient-caregiver relationships contribute to the adverse effects of caregiving. Aim 2 (Pathways): To explore behavioral and biological mechanisms underlying associations between emotional characteristics of patients, caregivers, and patient-caregiver relationships and adverse effects of caregiving. Aim 3 (Diagnosis): To determine the ways that patient diagnosis moderates the relationships among predictors, pathways, and outcomes in two major forms of dementia (AD and FTD). Aim 4 (Optimal measures): To determine: (a) the ?value-added? of our comprehensive biobehavioral assessments of emotional functioning compared to more commonly used questionnaires and tests, and (b) optimal sets of measures for predicting particular caregiver (e.g., declines in physical health; declines in mental health) and patient (i.e., mortality) outcomes. Significance: Identifying emotional characteristics of patients, caregivers, and patient-caregiver relationships that are associated with adverse effects of caregiving and the mechanisms that mediate these associations adds to our understanding of a growing public health problem and helps identify indicators of heightened vulnerability and targets for future interventions.